dl-tryptophane and processes for producing the same



product with Patented July 1, 19451 FUNITED I STATES ai-rarrro -Ii'le '1. Stiller.

PHANI AND PRODUCING m PATENT OFFICE mocsssas roa sans sew York, N. 1!.

No Drawing. .Appiieation June 8, 1041, Serial No. 386,829

4m...- (cum-s19) invention relates to improved for the production 01 dl-tryptophane.

Processes heretofore known for the production of dJ-tryptophane have had the disadvantales,

among others, that expensive starting' materials are utilized,-and low yields are obtained.

1 have now discovered that dl-tryptophane may be obtained in greatly increased yields by an improved process which involves the steps illustrated in the following how sheet:

NaOEt I FeSOfl no, N0| iollowedby estariiisstion Zn(GN)|. one NaOB om n-cent On no: cummqninolineiollowed coon .cooa: coon bydiLaeetieadd N N N a v y H r 02:0 4 Ado cn-o-c=o I cneo ooon NaOH ctmcomrcmcoon o -o mz-co-oa.

new

0 (as He lit) understood that this exampieis given by way of illustration and not of limitation.

imare by.

hoile solution with ethyl oxalate in the presence 01'' sodium ethylate, and treatinrthe reaction onium hydroxide in the presence'oi ferrous sulfate V followed by esteriilcaote), as m. of sinccyahide and 300 cc. or

anhydrous ether is plaoed in a flask fitted with an inlet tube, a reflux 'r fitted with an outlet tdbe to-a sulfuric acid trap, and

a stirrer. mixture is stirred'and cooled in an ice salt bath. Dry hydrogen chloride as is passed throuah the mixture: for 6 and $5 hours.

At the end or two the ice bath is substituted by a warm water bath. and the ether allowed to reflux sently. The mixture is .then

allowed to stand for $6 hour and then the. supernatant liquid is decanted from the solid which The following example illustrates a method 61 v carrying out the present invention. but it is to be OHr-CH-OOOH -co.-c.n|

armor-copper bronze. The mixture isheated atlas C. in an oil bath until all evolution or a carbon dioxide has ceased. During the reaction, the'copperdisappearsinpartresultinginthe formation of a green-colored solution indicating the formation. of .a' copper compound. Alternatively, the decarboxylation, may 'be accomplished by heating, in quinoline, the copper salt 01' 2-carboxy-indol-3 aldehyde anil. The copper bronze is removed by filtration, and washed with a mixture of quinoline and alcohol. Thecombined nitrate and washings are evaporated under reduced pressure, and the dry residue extracted twieej'with 500 cc. and 400 cc. portions oi 1.5% hot acetic acid and iiltered hot. The crude indol aldehyde crystallizes from the cold combined illtrates and is filtered oil. It is purified by recrys llization from 500 cc. of hot water (norite), M. P.'196-198 0. Further quantities or aidehyde' are obtained by working up themother liquo'ra. Indol-3-aldehyde is obtained in a yield at about 78%.

m-c -coon mom. B O

coal are added. The mixture is hydrogenated at atmospheric pressure until the theoretical amount of'hydrogen has been taken up (about eight hours) The catalyst is removed by filtration and washed with a little dilute ammonia. The filtrate is stirred and acidified with dilute hydrochloric acid whereupon a fine crystalline precipitate of dl-benzol tryptophane'forms. The

precipitate is filtered 011 and dried in vacuo; M. P.193-196" C. The benzoyl dl-tryptophane is obtained in a yield of over 89%.

2 gms. of dl-benzoyl tryptophane are refluxed with 100 cc. of 20% barium hydroxide solution until all of the solid has goneinto solution (about three hours). The mixture is refluxed for an additional half hour and while the. solution is still hot, itis poured into 100 cc. of water. The solution is made acid to Congo red with dilute sulfuric acid, the barium sulfate removed and the filtrate extracted with three 60 cc. portions of ether. The sulfate ion is then removed with barium hydroxide, the barium sulfate filtered off, and the filtrate concentrated to 200 cc. and again adjusted with sulfuric acid and barium hydroxide until no more precipitate forms. The concentration may be continued until the volume reaches '70 cc., when 300 cc. of ethyl alcohol are added. The mixture is placed in the refrigerator, and allowed to stand for spirit and scope thereof. and I am to be limited only by the appended claims. I claim:

1. In a process for the production of dltryptophane, the step comprising hydrogenating in the presence of palladium a compound selected from the group consisting of a-benzoylamino-p-indolyl-acrylic acid and its salts.

2. In a process for the production of dl-tryptophane, the step comprising hydrogenating in the presence of palladium the sodium salt of the u-benzoyl-amino-p-indolyl acrylic acid.

3. In a process for the production of dl-tryptophane, the step comprisinghydrogenating in the presence of palladium on charcoal a-benzoyl-amino-p-indolyl acrylic acid. a

v 4. In a process for the production of dl-tryptophane, the steps comprising hydrogenating, in

the presence of a palladium catalyst, a compound selected from the group consisting of a benzoyl-amino-p-indolyl-acrylic acid. and salts 30 thereof, recovering benzoyl-dl-tryptophane, and

hydrolyzing the latter to produce dl-tryptophane.

ERICT.STILLER.'- 

